Prediction of Hepatocellular Carcinoma by On-Therapy Response of Noninvasive Fibrosis Markers in Chronic Hepatitis B
Heechul Nam 1 , Sung Won Lee, Jung Hyun Kwon, Hae Lim Lee, Sun Hong Yoo, Hee Yeon Kim, Do Seon Song, Pil Soo Sung, U Im Chang, Chang Wook Kim, Soon Woo Nam, Si Hyun Bae, Jong Young Choi, Seung Kew Yoon, Jin Mo Yang, Nam Ik Han, Jeong Won Jang
Affiliations
Affiliation
1
Devision of Hepatology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea; The Catholic University Liver Research Center, Seoul, Republic of Korea.
PMID: 33734114 DOI: 10.14309/ajg.0000000000001219
Abstract
Introduction: Antiviral therapy improves hepatic fibrosis and reduces hepatocellular carcinoma (HCC) incidence. This study aimed to evaluate whether on-therapy changes in scores for fibrosis index based on 4 factors and aspartate aminotransferase-to-platelet ratio index are associated with HCC development and establish an HCC risk score model incorporating noninvasive fibrosis marker (NFM) response.
Methods: This multicenter study recruited 5,147 patients with chronic hepatitis B (4,028 for derivation cohort and 1,119 for validation cohort) who were given entecavir/tenofovir for >12 months between 2007 and 2018. A risk prediction model for HCC was developed using predictors based on multivariable Cox models, and bootstrapping was performed for validation.
Results: The 10-year cumulative HCC incidence rates were 12.6% and 13.7% in the derivation and validation cohorts, respectively. The risk of HCC significantly differed with early NFM response, with a marked reduction in HCC risk in patients achieving a significant decrease in NFM by 12 months (P < 0.001). NFM response, sex, age, and cirrhosis were independently predictive of HCC. We developed the Fibrosis marker response, Sex, Age, and Cirrhosis (FSAC) score based on regression coefficients of each variable. For the 10-year prediction of HCC, FSAC showed higher C-index values than PAGE-B, modified PAGE-B, CU-HCC, and REACH-B (0.84 vs 0.77, 0.80, 0.77, and 0.67, respectively; all P < 0.005). The predictive performance of FSAC was corroborated in the validation cohort, with higher C-index than other models (all P < 0.050).
Discussion: On-therapy changes in NFM are an independent indicator of HCC risk. FSAC incorporating NFM response is a reliable risk score for risk estimation for HCC with better performance than other models.